While the panel unanimously agreed the technology is effective, the majority did not believe there is reasonable assurance of the safety of the Medtronic Phased RF ablation system, and that the clinical benefits of the technology do not outweigh the potential risks based on the TTOP-AF clinical trial data.

Before the panel convened, the FDA released a report stating that the primary efficacy endpoints were met during the trial evaluating the device, but safety endpoints were not, making the agency question the device’s safety.

The committee recommendation will be considered by the FDA as it reviews the pre-market approval application for the Medtronic Phased RF Ablation System. The regulatory agency is not bound to accept the committee's recommendation, but typically does.

Minnesota-based Medtronic submitted a modular pre-market approval application with the last submission completed in June based on data from its TTOP-AF (Tailored Treatment of Persistent-AF) clinical trial, a randomized study comparing ablation therapy with traditional medical management (antiarrhythmic drugs and direct current cardioversion) in patients with persistent or long-standing persistent AF.

“While we are disappointed with [the] outcome, Medtronic looks forward to continuing discussions with the FDA to determine the best path forward,” Reggie Groves, vice president and general manager of Medtronic’s AF Solutions business, said in a statement.

Currently, the only FDA approved AF ablation medical devices are indicated for the treatment of paroxysmal AF, in which irregular heartbeats in the upper chambers start and stop suddenly on their own, usually for minutes or days at a time. As the disease progresses into persistent (recurrent episodes that last more than seven days) or long-standing persistent (continuous episodes that last more than one year) AF, it becomes more complex to treat. Persistent AF patients often have increased hospitalizations and healthcare costs, and the condition is more debilitating in terms of quality of life.

Results from the TTOP-AF clinical trial were presented on Oct. 10 at Venice Arrhythmias 2011, the 12th International Workshop on Cardiac Arrhythmias. The study met its chronic effectiveness endpoint, demonstrating that 55.8 percent of patients treated with the Medtronic Phased RF Ablation System had an AF and atrial flutter burden reduction of greater than 90 percent and were free from antiarrhythmic drug therapy at six months, compared with 26.4 percent in the traditional medical management arm. When including patients still on antiarrhythmic drug therapy following the procedure with the ablation system, 67.4 percent had a greater than 90 percent reduction of AF burden at six months.

The acute safety event rate in the trial was 12.3 percent with an upper 95 percent confidence interval of 19 percent, which did not meet the pre-defined performance goal of 16 percent. According to Medtronic, at the time of trial design, “no benchmark for the persistent AF patient population existed, so the performance goal of 16 percent was established based on a literature review evaluating ablation procedures in paroxysmal AF ablation patients.”

The Medtronic Phased RF Ablation System is investigational in the U.S., and currently approved for use in areas of Europe, Asia and Africa, as well as in Canada. More than 13,000 patients in 24 countries have been treated with the system since January 2009.